Department of Gastric Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China.
Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, Guangdong, P. R. China.
Cancer Commun (Lond). 2023 Dec;43(12):1312-1325. doi: 10.1002/cac2.12494. Epub 2023 Oct 14.
Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC). Here, we aimed to evaluate the predictive value of ctDNA in this context.
From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612). Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer-related genes. The plasma was defined as ctDNA-positive only if one or more variants detected in the plasma were presented in at least 2% of the primary tumors.
Compared with ctDNA-negative patients, patients with positive postoperative ctDNA had moderately higher risk of recurrence [hazard ratio (HR) = 2.74, 95% confidence interval (CI) = 1.37-5.48; P = 0.003], while patients with positive post-ACT ctDNA showed remarkably higher risk (HR = 14.99, 95% CI = 3.08-72.96; P < 0.001). Multivariate analyses indicated that both postoperative and post-ACT ctDNA positivity were independent predictors of recurrence-free survival (RFS). Moreover, post-ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and serial cancer antigen. A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C-index (0.78; 95% CI = 0.71-0.84) than the model without ctDNA (0.71; 95% CI = 0.64-0.79; P = 0.009).
Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC, and the combination of tissue-based and circulating tumor features could achieve better risk prediction.
循环肿瘤 DNA（ctDNA）是预测多种实体瘤复发的有前途的生物标志物。然而，ctDNA 对局部胃（GC）区域复发的预测价值仍不确定。在这里，我们旨在评估这种情况下 ctDNA 的预测价值。
从 2016 年到 2019 年，这项前瞻性队列研究（NCT02887612）招募了 100 名 II/III 期可切除 GC 患者。在手术切除期间采集原发性肿瘤，在围手术期和辅助化疗（ACT）后 3 个月内采集血浆样本。通过靶向 425 个癌症相关基因的测序面板捕获体细胞变体。仅当血浆中检测到的一个或多个变体在至少 2%的原发性肿瘤中存在时，才将血浆定义为 ctDNA 阳性。
与 ctDNA 阴性患者相比，术后 ctDNA 阳性患者复发的风险略高（风险比[HR] = 2.74，95%置信区间[CI] = 1.37-5.48；P = 0.003），而 ACT 后 ctDNA 阳性患者的风险明显更高（HR = 14.99，95%CI = 3.08-72.96；P < 0.001）。多变量分析表明，术后和 ACT 后 ctDNA 阳性均是无复发生存（RFS）的独立预测因子。此外，ACT 后 ctDNA 比术后 ctDNA 和连续癌抗原具有更好的预测性能（灵敏度，77.8%；特异性，90.6%）。纳入 ctDNA 进行复发风险预测的综合模型显示出更高的 C 指数（0.78；95%CI = 0.71-0.84），高于不包含 ctDNA 的模型（0.71；95%CI = 0.64-0.79；P = 0.009）。
ACT 后残留的 ctDNA 有效地预测了 II/III 期 GC 的高复发风险，并且组织和循环肿瘤特征的结合可以实现更好的风险预测。
